2-Bromo-6-[¹⁸F]fluoropyridine: Two-step fluorine-18 radiolabelling via transition metal-mediated chemistry

Novel radiolabelling methods are important for the development of new tracers for positron emission tomography. Direct nucleophilic fluorination of aromatic rings with [¹⁸F]fluoride is limited to activated substrates, restricting the application of this approach. Inspired by transition metal-mediated transformations, a fluorine-18 synthon was prepared to supplement the radiolabelling methods available for molecules unsuitable for direct labelling. 2-Bromo-6-[¹⁸F]fluoropyridine (denoted [¹⁸F]1) was prepared in high yield, and palladium-mediated cross-coupling reactions were exemplified. High incorporation of fluoride and efficient cross-coupling reactions demonstrate that compound [¹⁸F]1 holds promise as a new synthon for construction of fluorine-18-labelled molecules via transition metal-mediated reactions.